ArticleDevelopment (Cambridge, England)2014
Simultaneous rather than ordered cleavage of two sites within the BMP4 prodomain leads to loss of ligand in mice.
Article in Development (Cambridge, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
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Who cites it
13 citing papers in PubMed.
- Article
- Microvilli control the morphogenesis of the tectorial membrane extracellular matrix.Developmental cell · 2025Article
- The prodomain of bone morphogenetic protein 2 promotes dimerization and cleavage of BMP6 homodimers and BMP2/6 heterodimers.The Journal of biological chemistry · 2024Article
- Microvilli regulate the release modes of alpha-tectorin to organize the domain-specific matrix architecture of the tectorial membrane.bioRxiv : the preprint server for biology · 2024Article
- Lack of evidence that fibrillin1 regulates bone morphogenetic protein 4 activity in kidney or lung.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Molecular Mechanisms of AMH Signaling.Frontiers in endocrinology · 2022Review
- Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos.Journal of visualized experiments : JoVE · 2021Article
- Review
- BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis.eLife · 2019Article
- Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.The Journal of biological chemistry · 2017Article
- Structural Biology and Evolution of the TGF-β Family.Cold Spring Harbor perspectives in biology · 2016Review
- Posttranslational processing of FGF23 in osteocytes during the osteoblast to osteocyte transition.Bone · 2016Article
- The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
ProBMP4 is generated as a latent precursor that is sequentially cleaved at two sites within the prodomain to generate an active ligand. An initial cleavage occurs adjacent to the ligand domain, which generates a non-covalently associated prodomain/ligand complex that is subsequently dissociated by cleavage at an upstream site. An outstanding question is whether the two sites need to be cleaved sequentially and in the correct order to achieve proper control of BMP4 signaling during development. In the current studies, we demonstrate that mice carrying a knock-in point mutation that causes simultaneous rather than sequential cleavage of both prodomain sites show loss of BMP4 function and die during mid-embryogenesis. Levels of mature BMP4 are severely reduced in mutants, although levels of precursor and cleaved prodomain are unchanged compared with wild type. Our biochemical analysis supports a model in which the transient prodomain/ligand complex that forms during sequential cleavage plays an essential role in prodomain-mediated stabilization of the mature ligand until it can acquire protection from degradation by other means. By contrast, simultaneous cleavage causes premature release of the ligand from the prodomain, leading to destabilization of the ligand and loss of signaling in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.